The objective of the proposed research is to explore endocannabinoid-immunophilin signaling during embryo implantation using mice as an animal model. Cannabinoids exert a broad array of effects, including fertilization, embryo development, and implantation. Our lab has shown that uterine anandamide levels are tightly regulated during implantation, with lower levels conducive and higher levels detrimental. Functions of ovarian estrogen and progesterone are essential to implantation and pregnancy establishment and executed primarily via their cognitive nuclear receptors. FKBP52, an immunophilin, functions as a co-chaperone for nuclear steroid receptors and is required for their normal functioning. Female Fkbp52 null mice are infertile because of implantation failure resulting from compromised progesterone receptor function. Using multiple approaches, we will explore whether endocannabinoid signaling collaborates with that of immunophilin in rendering the uterus receptive for implantation with the eventual goal of determining whether the anandamide index serves as a marker of uterine receptivity. Widespread marijuana use and its known adverse effects on reproduction classifies this research as highly relevant to women's health issues. [unreadable] [unreadable] [unreadable]